Solid experimental data links human autoimmune thyroid disease (AITD) and expression of chemokines, but the studies to date have been mostly descriptive. We have developed transgenic models to investigate the role of chemokines in AITD. We have reported that expression of CCL21, a chemokine expressed in AITD, leads to recruitment of lymphocytes and dendritic cells (DC) into the thyroid. As is found in AITD, lymphocytes organize in structures resembling lymphoid follicles, in which vascular structures such as high endothelial venules (HEV) and lymphatics are present. Deletion of CCR7, the receptor for CCL21, in the autoimmune-prone NOD background favors development of thyroiditis, suggesting a regulatory role for CCL21 in AITD.
Our specific aims i n this proposal are: 1) to define the mechanisms favoring the formation of thyroid lymphoid follicles, and their relevance to development of EAT;and 2), to define the mechanisms favoring development of thyroiditis in NODCCR7ko/ko mice. Many types of thyroid diseases are caused by destruction of the cells of the thyroid by cells of the immune system. PUBLLIC

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We will investigate the mechanisms whereby these immune cells arrive in the thyroid and will determine if blocking some of these mechanisms will alter thyroid disease. This work should define the role of immune components in the pathogenesis of thyroid diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Integrative and Clinical Endocrinology and Reproduction Study Section (ICER)
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Spain, Lisa M
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Icahn School of Medicine at Mount Sinai
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Lira, Sergio A; Furtado, Glaucia C (2012) The biology of chemokines and their receptors. Immunol Res 54:111-20
Muniz, Luciana R; Pacer, Michelle E; Lira, Sergio A et al. (2011) A critical role for dendritic cells in the formation of lymphatic vessels within tertiary lymphoid structures. J Immunol 187:828-34
Viejo-Borbolla, A; Martin, A P; Muniz, L R et al. (2010) Attenuation of TNF-driven murine ileitis by intestinal expression of the viral immunomodulator CrmD. Mucosal Immunol 3:633-44
Shang, Limin; Thirunarayanan, Nanthakumar; Viejo-Borbolla, Abel et al. (2009) Expression of the chemokine binding protein M3 promotes marked changes in the accumulation of specific leukocytes subsets within the intestine. Gastroenterology 137:1006-18, 1018.e1-3
Furtado, Glaucia C; Marinkovic, Tatjana; Martin, Andrea P et al. (2007) Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. Proc Natl Acad Sci U S A 104:5026-31
Marinkovic, Tatjana; Garin, Alexandre; Yokota, Yoshifumi et al. (2006) Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid. J Clin Invest 116:2622-32
Furtado, Glaucia C; Pina, Beatrice; Tacke, Frank et al. (2006) A novel model of demyelinating encephalomyelitis induced by monocytes and dendritic cells. J Immunol 177:6871-9
Lira, Sergio A; Martin, Andrea P; Marinkovic, Tatjana et al. (2005) Mechanisms regulating lymphocytic infiltration of the thyroid in murine models of thyroiditis. Crit Rev Immunol 25:251-62
Martin, Andrea P; Coronel, Elizabeth C; Sano, Gen-ichiro et al. (2004) A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21. J Immunol 173:4791-8